Heat shock cognate-70 gene expression declines during normal aging of the primate retina

PURPOSE. Despite documented age-related changes in retinal function and his tology, little is known about the pattern of gene expression during normal aging of the vertebrate retina. This study was undertaken to definitively c haracterize gene expression in the primate retina during aging. METHODS. Human retina cDNA library clones were arrayed at high density on n ylon membranes and screened with mixed cDNA probes generated from young (4- year-old) and old (80-year-old) human retinae. Clones showing a more than t wofold difference in intensity were rescreened by dot blot analysis with th e same probes and with mixed cDNA probes generated from young (2-3 years) a nd old (27-35 years) rhesus monkeys. One clone identified by its differenti al (age-putative) signal, and age-related differential expression was used for analysis of Northern blot analysis of total retinal RNA from human dono rs (35 weeks to 94 years of age) and two rhesus monkeys (2 and 27 years of age). The identified clone was sequenced and compared with entries in the G enBank/EMBL databases. Western blot analysis was performed on protein isola ted from the retina of human donors aged 4 to 64 years and rhesus monkeys a ged 18 months and 35 years. RESULTS. Approximately 1.6% of the 55,368 retina-expressed sequences examin ed show age-related changes between tissues from young and old donors. The mRNA level one clone, identical with heat shock cognate (HSC)70, was altere d during normal retinal aging in primates. Regression analysis of Northern blot analysis signals from 23 human donors suggested that there may be a tw o-to threefold decrease in HSC70 mRNA levels in the human retina by the eig hth decade of life. Western blot analysis also showed lower levels of the 7 0-kDa HSC protein in older tissues of both primates. CONCLUSIONS. HSC70 mRNA levels apparently decline during normal aging of th e primate retina. Because the hear shock 70 protein family may play importa nt roles in ocular development and protection from various biologic and env ironmental stresses, decreased HSC70 levels in the retina during aging may contribute to the apparent. increased susceptibility of the retina to age-a cquired retinal disease.